title: [Current status and future prospects of stem cell gene therapy for primary immunodeficiency].
abstract: Patients affected by primary immunodeficiency (PID) can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). In the absence of HLA-matched donors, however, incidence of HSCT-related complications is observed. Therefore, gene therapy has been developed as a highly desirable alternative treatment for patients lacking suitable donors. Retrovirus-based gene therapy was begun in 1990 for the patients of adenosine deaminase deficiency, followed by X-linked severe combined immunodeficiency, Wiskott-Aldrich syndrome and chronic granulomatous disease. Although treated patients have had excellent immune reconstitution and resolution of ongoing infections, complications such as a lymphoproliferative syndrome and a disappearance of gene-modified cells were observed in some clinical trials. To overcome these, ongoing and upcoming clinical trials use some new strategies. The use of preconditioning chemotherapy makes space in the bone marrow for the gene-treated stem cells and allows engraftment of multi lineage stem/progenitor cells. Self-inactivating vectors in which strong enhancers of long terminal repeat are eliminated may reduce the risk of insertional activation of proto-oncogene resulting in leukemia. These modifications will surely increase the safety and efficacy of stem cell gene therapy for PID.
authors.affiliation: Department of Human genetics, National Center for Child Health and Development.
authors.forename: Toru
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Masafumi
authors.initials: M
authors.lastname: Onodera
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency; D000361:Agammaglobulinemia / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods*; D006105:Granulomatous Disease, Chronic / Q000628:therapy; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000628:therapy*; D000090063:Proto-Oncogene Mas; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D013234:Stem Cells; D014923:Wiskott-Aldrich Syndrome / Q000628:therapy
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D000243:Adenosine Deaminase